Faculty

Schulich School of Medicine & Dentistry

Supervisor Name

Dr. Jessica Prodger

Keywords

Mucosa, SARS-CoV-2, Nasal organotypic model, Microbiome, Immunology

Description

The microbiota is essential to the functioning of the immune system. The nasal milieu secretes immune molecules that can be influenced by diverse bacteria. Hence commensals that enhance anti-viral responses may confer resistance to respiratory viral infection.

Our collaborators have identified 7 microbial state types (CST) defined by indicator species in the nose and recently, through analyses of nasal immune molecules, we have categorized the nasal immune profile types into 8 groups (IPT). Although the IPTs correlated with certain CSTs, the influence of the nasal microbiome on susceptibility to respiratory pathogens is still unknown.

Defining this complex relationship requires a relevant in vitro model which recapitulates key aspects of the in vivo nasal epithelium (pseudostratification, mucociliary differentiation), can sustain stable bacterial communities in a relevant environment (air-interfaced), and can support infection with respiratory pathogens (e.g., Staphylococcus aureus, influenza, SARS-CoV-2). Conventionally cultured cells lack innate protective features such as mucus and cilia and do not express physiological levels of innate immune mediators or pathogen entry receptors. These epithelial characteristics are crucial to reconstruct the complexity of microbiome-host-pathogen interactions in a controlled in vitro model. We have previously developed a nasal model capable of being infected by SARS-CoV-2, however due to variability in the source of cells, maintenance of culture consistency was difficult to achieve. Some obstacles included nonviable cells at isolation, fibroblast contaminations, and early death of differentiated cells.

Hypothesis: In this study, we aim to optimize our current nasal model to provide consistent cell cultures to support bacterial co-cultures and SARS-CoV-2 infection studies.

Acknowledgements

We want to sincerely thank all tissue donors. Thanks to our collaborators for assisting in tissue collection and performing viral challenges on our model. Thanks to my supervisor Dr. Jessica Prodger for her continued support and guidance, and all the members of our lab. Thank you to the department of Microbiology and Immunology. Thank you to Western University USRI for funding the internship.

Creative Commons License

Creative Commons Attribution-Noncommercial 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License

Document Type

Poster

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Developing a Nasal Organotypic Model to Investigate the Effects of the Nasal Microbiome on Susceptibility to Pathogens

The microbiota is essential to the functioning of the immune system. The nasal milieu secretes immune molecules that can be influenced by diverse bacteria. Hence commensals that enhance anti-viral responses may confer resistance to respiratory viral infection.

Our collaborators have identified 7 microbial state types (CST) defined by indicator species in the nose and recently, through analyses of nasal immune molecules, we have categorized the nasal immune profile types into 8 groups (IPT). Although the IPTs correlated with certain CSTs, the influence of the nasal microbiome on susceptibility to respiratory pathogens is still unknown.

Defining this complex relationship requires a relevant in vitro model which recapitulates key aspects of the in vivo nasal epithelium (pseudostratification, mucociliary differentiation), can sustain stable bacterial communities in a relevant environment (air-interfaced), and can support infection with respiratory pathogens (e.g., Staphylococcus aureus, influenza, SARS-CoV-2). Conventionally cultured cells lack innate protective features such as mucus and cilia and do not express physiological levels of innate immune mediators or pathogen entry receptors. These epithelial characteristics are crucial to reconstruct the complexity of microbiome-host-pathogen interactions in a controlled in vitro model. We have previously developed a nasal model capable of being infected by SARS-CoV-2, however due to variability in the source of cells, maintenance of culture consistency was difficult to achieve. Some obstacles included nonviable cells at isolation, fibroblast contaminations, and early death of differentiated cells.

Hypothesis: In this study, we aim to optimize our current nasal model to provide consistent cell cultures to support bacterial co-cultures and SARS-CoV-2 infection studies.

 

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